Department of Integrative Medical Biology, Umeå University, Biologihuset, S-901 87 Umeå, Sweden.
Prog Neurobiol. 2010 Feb 9;90(2):190-7. doi: 10.1016/j.pneurobio.2009.10.009. Epub 2009 Oct 21.
Grafting of dopamine-rich tissue to counteract the symptoms in Parkinson's disease became a promising tool for future treatment. This article discusses how to improve the functional outcome with respect to graft outgrowth and functions of dopamine release and electrophysiological responses to graft implantation in the host brain striatal target. It has been documented that a subpopulation of the dopamine neurons innervates the host brain in a target-specific manner, while some of the grafted dopamine neurons never project to the host striatum. Neurochemical studies have demonstrated that the graft-induced outgrowth synthesize, store, metabolize and release dopamine and possibly other neurotransmitters such as 5-HT. Furthermore, the released dopamine affects the dopamine-depleted brain in areas that are larger than the graft-derived nerve fibers reach. While stem cells will most likely be the future source of cells to be used in grafting, it is important to find the guiding cues for how to reinnervate the dopamine-depleted striatum in a proper way with respect to the dopamine subpopulations of A9 and A10 to efficiently treat the motor abnormalities seen in Parkinson's disease.
将富含多巴胺的组织移植到帕金森病患者体内以缓解症状,这一方法成为未来治疗的一种有前途的手段。本文探讨了如何改善移植体的功能,包括其在宿主大脑纹状体靶区的生长情况以及多巴胺释放和电生理反应的功能。有文献记载,多巴胺神经元的一个亚群以特定的靶区方式支配宿主的大脑,而一些移植的多巴胺神经元从未投射到宿主纹状体。神经化学研究表明,移植诱导的生长合成、储存、代谢和释放多巴胺,并且可能释放其他神经递质,如 5-HT。此外,释放的多巴胺会影响到比移植源性神经纤维到达的区域更大的多巴胺耗竭的大脑区域。虽然干细胞很可能成为未来用于移植的细胞来源,但找到正确的神经再支配线索对于有效地治疗帕金森病患者的运动异常非常重要,这些线索涉及 A9 和 A10 多巴胺亚群,以便适当地再支配多巴胺耗竭的纹状体。